Cited 19 time in webofscience Cited 24 time in scopus

Evolution of the multi-tRNA synthetase complex and its role in cancer

Title
Evolution of the multi-tRNA synthetase complex and its role in cancer
Authors
Hyeon, Do YoungKim, Jong HyunAhn, Tae JinCho, YeshinHwang, DaeheeKim, Sunghoon
DGIST Authors
Hwang, Daehee
Issue Date
2019-04
Citation
Journal of Biological Chemistry, 294(14), 5340-5351
Type
Article
Article Type
Review
Author Keywords
aminoacyl tRNA synthetaseprotein synthesisintracellular processingpathologycancer biologyAminoacyl-tRNA synthetasesCancermulti-tRNA synthetase complexnetwork analysisprotein-protein interaction
Keywords
PROTEIN-PROTEIN INTERACTIONSMULTISYNTHETASE COMPLEXTRANSLATIONAL CONTROLGENEIDENTIFICATIONAUTOANTIBODIESDISSECTIONPHOSPHORYLATIONDERMATOMYOSITISHETEROGENEITY
ISSN
0021-9258
Abstract
Aminoacyl-tRNA synthetases (ARSs) are enzymes that ligate their cognate amino acids to tRNAs for protein synthesis. However, recent studies have shown that their functions are expanded beyond protein synthesis through the interactions with diverse cellular factors. In this review, we discuss how ARSs have evolved to expand and control their functions by forming protein assemblies. We particularly focus on a macromolecular ARS complex in eukaryotes, named multi-tRNA synthetase complex (MSC), which is proposed to provide a channel through which tRNAs reach bound ARSs to receive their cognate amino acid and transit further to the translation machinery. Approximately half of the ARSs assemble into the MSC through cis-acting noncatalytic domains attached to their catalytic domains and trans-acting factors. Evolution of the MSC included its functional expansion, during which the MSC interaction network was augmented by additional cellular pathways present in higher eukaryotes. We also discuss MSC components that could be functionally involved in the pathophysiology of tumorigenesis. For example, the activities of some trans-acting factors have tumor-suppressing effects or maintain DNA integrity and are functionally compromised in cancer. On the basis of Gene Ontology analyses, we propose that the regulatory activities of the MSC-associated ARSs mainly converge on five biological processes, including mammalian target of rapamycin (mTOR) and DNA repair pathways. Future studies are needed to investigate how the MSC-associated and free-ARSs interact with each other and other factors in the control of multiple cellular pathways, and how aberrant or disrupted interactions in the MSC can cause disease. © 2019 Hyeon et al.
URI
http://hdl.handle.net/20.500.11750/9818
DOI
10.1074/jbc.REV118.002958
Publisher
American Society for Biochemistry and Molecular Biology Inc.
Files:
There are no files associated with this item.
Collection:
Department of New BiologySystems Biology and Medicine Lab1. Journal Articles


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